Subsequent evaluation of once-daily doses of verubecestat in Phase 1 studies of healthy volunteers and in people with AD for a duration of one week demonstrated significant decreases in the levels of Aß peptide production, a key marker of BACE1 activity, in the cerebral spinal fluid (CSF) of up to 80 percent. Data from patients with AD were initially presented at the 2013 Alzheimer's Association International Conference (AAIC).Results of the Phase 1 trial of patients with Alzheimer's disease The randomized, double-blind, placebo-controlled multiple dose study evaluated the safety and tolerability, pharmacokinetics and pharmacodynamic profile of verubecestat in patients with mild-to-moderate Alzheimer's disease (n=32). Patients were randomized to receive one of three doses (12 mg, 40 mg and 60 mg) of verubecestat or placebo orally once-daily for seven days. Samples of CSF were collected over 36 hours via a lumbar catheter and analyzed for levels of amyloid ß 40 (Aß40), amyloid ß 42 (Aß42) and soluble amyloid precursor protein ß (sAPPß) as biomarkers of BACE1 activity. In this study, verubecestat at doses of 12, 40 and 60 mg caused a dose-dependent and sustained reduction in the levels of Aß40 from baseline in the CSF, a measure of BACE1 activity, of 57, 79 and 84 percent, respectively. No study discontinuations due to adverse events were recorded. Analysis of vital signs and laboratory assessments, including liver function tests, showed no statistically significant changes related to the administration of verubecestat. Verubecestat was generally well-tolerated in healthy volunteers and individuals with AD. No dose-dependent increase in the incidence of adverse events was observed. Adverse events included headache, nasal congestion and dizziness. About the EPOCH Study EPOCH is a Phase 2/3 randomized, placebo-controlled, parallel-group, double-blind study evaluating efficacy and safety of two oral doses of verubecestat (12 mg and 40 mg) administered once-daily versus placebo in patients with mild-to-moderate AD currently using standard of care treatment. The primary efficacy outcomes of the study are the change from baseline in the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) score, as well as the change from baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) score, following 78 weeks of treatment. For more information about the EPOCH study, visit www.merck.com/clinical-trials/infographics/P07738.html. About the APECS Study APECS is a randomized, placebo-controlled, parallel-group, double-blind Phase 3 clinical trial to evaluate the efficacy and safety of verubecestat in subjects with prodromal AD. The study is designed to enroll 1,500 participants. Patients will be randomized to receive placebo, or 12 mg or 40 mg verubecestat, once-daily. The primary efficacy outcome of the study is change from baseline in the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) score following 104 weeks of treatment. About Merck For 125 years, Merck has been a global health care leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook, YouTube and LinkedIn. Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the "company") includes "forward-looking statements" within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company's management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company's 2015 Annual Report on Form 10-K and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site ( www.sec.gov).